Antihyperglycemic Medication to Combat Skin AGE-ing

April 2024 | Volume 23 | Issue 4 | 289 | Copyright © April 2024


Published online March 23, 2024

Cleo Whiting BAa, Sara Abdel Azim MSa,b, Adam Friedman MD FAADa

aDepartment of Dermatology, George Washington University School of Medicine and Health Sciences, Washington, DC
bGeorgetown University School of Medicine, Washington, DC

attenuated photoaging due to UVA irradiation through reduced ROS accumulation and mitophagy, and the attenuation of the DNA-repairing phosphatidylinositol 3-kinases (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathways11; in vivo, UVA-irradiated mice treated with 10 mg/kg/day of metformin showed decreased signs of skin photoaging grossly and histologically and had significantly decreased expression of MMP1 and the mitophagy protein Parkin.11 Similarly, signs of UVB-induced photoaging were attenuated following the topical application of 0.6% metformin cream to mice skin.12 Furthermore, in vitro studies exploring the effects of 50 microM and 500 microM metformin on the viability of fibroblasts under high-glucose conditions (50 microM) found both doses of metformin significantly downregulated NF-kB (p65) activity, inhibited apoptosis of fibroblasts, and increased production of collagen I-III compared to control.13,14 Altogether, metformin appears to have protective properties against two major sources of skin aging, UVR-damage and AGEs.

Glucagon-Like Peptide-1 Receptor Agonists
Indicated for type 2 diabetes and weight management, GLP-1 RAs increase incretin hormones and glucose-dependent insulin release, decrease glucagon secretion, and reduce gastric emptying.15 Given the similar antihyperglycemic effect of metformin, it is logical to suspect GLP-1 RAs may also have similar anti-aging effects. Indeed, multiple clinical trials demonstrated that GLP-1 RAs delay and treat age-related diseases, including osteoporosis, Parkinson's disease, atherosclerosis, kidney diseases, and non-alcoholic fatty liver disease.3 GLP-1 RAs also ameliorate psoriasis by inhibiting generation of inflammatory cytokines.16,17 Though GLP-1 RAs have not been studied within the context of skin aging, chronic inflammation is a known driver of skin aging as discussed above18; thus the anti-inflammatory benefits of GLP-1 RAs may curtail skin aging, namely through reduction of deleterious AGEs. Notably, GLP-1 RAs have demonstrated efficacy in diabetic rat wounds, significantly reducing C-reactive protein concentrations and MMP-9/tissue matrix metalloproteinase inhibitor-1 ratios in fibroblast cultures, reflecting increased expression of anti-inflammatory and pro-healing markers.19 Purposeful studies on the effects of GLP-1 RAs and their impact on skin aging specifically are necessary to fully establish a relationship.

CONCLUSION
While the role of antihyperglycemic drugs such as metformin and GLP-1 RAs in combatting skin aging has yet to be fully described, dermatologists should be aware of the underlying mechanisms of these drugs and anticipate their potential inclusion in future armamentariums. 

DISCLOSURE
CW's work is funded through an independent fellowship grant from Galderma; SAA's work is funded through independent fellowship grants from Lilly and Pfizer. AF has no conflicts of interest to declare. 

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AUTHOR CORRESPONDENCE

Adam Friedman MD FAAD ajfriedman@mfa.gwu.edu
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